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Paradoxical resistance to high fat diet-induced obesity
and altered macrophage polarization in
mineralocorticoid receptor overexpressing mice.
Emmanuelle Kuhn, Christine Bourgeois, Vixra Keo, Say Viengchareun,
Adeline Muscat, Geri Meduri, Damien Le Menuet, Bruno Fève, Marc Lombes
To cite this version:
Emmanuelle Kuhn, Christine Bourgeois, Vixra Keo, Say Viengchareun, Adeline Muscat, et al.. Paradoxical resistance to high fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor overexpressing mice.: MR overexpression and adipocyte differentiation. AJP - Endocrinology and Metabolism, American Physiological Society, 2014, 306 (1), pp.E75-90. �10.1152/ajpendo.00323.2013�. �inserm-00911857�
A
170 130 100 55 WT Tg 0 0.5 1 1.5 2 2.5 3 3.5 4 M R /α-tu bu linB
0 0.2 0.4 0.6 0.8 1 1.2 1.4 R el at iv e Ex pr es si on (m M R /1 8S )mMR
WT HFD
Tg HFD
0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e Ex pr es si on (h M R /1 8S )hMR
***
*
MR α-tubulin kDaAdipose tissue
Isolated Adipocytes
Adipose tissue
0 0.2 0.4 0.6 0.8 1 1.2 1.4
D
E
C
hMR
***
WT Tg WT Tg WT Tg Tg WT R el at iv e Ex pr es si on (h M R /1 8S )Figure 1
MR
+
preadipocyte
adipocyte
In Vitro/Ex vivo
macrophage
In Vivo
MR
M1-like macrophages
InflammationM2-like macrophages
Alternative activationMR
A
B
Basal Medium Control Medium
CM WT CM Tg
C
0 0.2 0.4 0.6 0.8 1.0 1.2 BasalMedium MediumControl WT CM Tg CM
R el at iv e ex pr es si on (P P A R γ2 /1 8S ) Basal Medium Control Medium WT CM Tg CM
***
***
p=0.08PPARγ2
0 0.2 0.4 0.6 0.8 1.0 1.2 BasalMedium MediumControl
R el at iv e E xp re ss io n (F A S /1 8S )
*
***
***
FAS
WT CM Tg CMA
x10 x10 x40 x40 WT Tg 0 2 4 6 8 +++ ++ + _ nu m be r of a ni m als (-) (+++) +_B
0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e ex pr es si on F4 /8 0/ 18 S 0 0.5 1 1.5 R el at iv e ex pr es si on (h M R /1 8S )***
F4/80
hMR
WT Tg WT Tg WT TgC
*
0 5 10 15 20 WT TgGonadal SVF
FSC F4/80D
0% 25% 50% 75% 100% WT Tg CD11c+ DP CD206+ DN CD11c CD 206 CD11c WT Tg CD206+ CD11c+ DP CD206+ CD11c+ DP C D20 6E
0 0.2 0.4 0.6 0.8 1.0 R el at iv e ex pr es si onF4/80
***
***
‡‡‡ ‡‡‡ 0 0.1 0.2 0.3 0.4CD206
***
**
‡ 0 0.05 0.10 0.15 0.20 0.25 0.30CD11c
***
** ‡‡‡ ‡‡‡ SC HFD SC HFD SC HFD WT Tg WT Tg WT Tg WT Tg WT Tg WT Tg WT Tg F4/80 expressing cells (%) NS 0 2 4 6 8 10 12 14 16 F4 /8 0 ex pr es si ng ce lls (% )Spleen
**
NS WT Tg WT Tg HFD SC HFDR el at iv e Ex pr es si on (mMR/18S) 0 0.5 1.0 1.5 2.0 2.5 R el at iv e Ex pr es si on (P PA R γ2 /1 8S )
PPARγ2
0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0mMR
WT
Tg
WT Tg WI WP WG Basal Condition Differentiation CocktailA
B
C
**
**
*
WI WP WG WI WP WGFigure 7
0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e ex pr es si on (P P A R γ2 /1 8S )
PPARγ2
WT
0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e ex pr es si on (G R /1 8S )GR
0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e ex pr es si on (1 1β H S D 1/ 18 S )11βHSD1
0 0.2 0.4 0.6 0.8 1 1.2 0 0.2 0.4 0.6 0.8 1 1.2*
*
0 0.2 0.4 0.6 0.8 1 1.2***
*
**
SC
Tg
WT
HFD
A
B
C
D
E
F
Tg
WT
WT
WT
WT
WT
Tg
Tg
Tg
Tg
Tg
R el at iv e ex pr es si on (P P A R γ2 /1 8S ) R el at iv e ex pr es si on (G R /1 8S ) R el at iv e ex pr es si on (1 1β H S D 1/ 18 S )A
0 2 4 6 8 10 12 14 16 18 % a di po cy te s pe r cl as s adipocyte surface (x103µm2)WT HFD
Tg HFD
0 10 20 30 40 50 60 70 80 % a di po cy te p er c la ssDistribution of adipocyte surface
WT SC
Tg SC
30B
p<0.0001 p<0.0001Figure 5
100µm x10 x10 x10WT
Tg
SC
HFD
0 50 100 150 200 250 300 350 400 0 15 30 45 60 90 120 G ly ce m ia (m g/ dl ) Time (min)
WT HFD
Tg HFD
A
0 20 40 60 80 100 120 0 15 30 45 60 90 120 % o f g ly ce m ia a t T 0 Time (min)WT HFD
Tg HFD
B
*
**
**
C
0 5 10 15 20 25 30 35 WT HFD Tg HFD AUC OGTT*
0 0.1 0.2 0.3 0.40.5 0.6 0.7 0.80.9 Weight (g )